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The antitumor compound triazoloacridinone C-1305 inhibits FLT3 kinase activity and potentiates apoptosis in mutant FLT3-ITD leukemia cells.
Conclusion:C-1305 induces apoptosis in FLT3-ITD-expressing human leukemia cells in vitro, suggesting that mutated FLT3 kinase can be a new target for C-1305, and C-1305 may be a drug candidate for the therapeutic intervention in FLT3-associated AML. PMID: 25640477 [PubMed - as supplied by publisher]
Source: Acta Pharmacologica Sinica - February 2, 2015 Category: Drugs & Pharmacology Authors: Augustin E, Skwarska A, Weryszko A, Pelikant I, Sankowska E, Borowa-Mazgaj B Tags: Acta Pharmacol Sin Source Type: research

Mechanism of synergy of BH3 mimetics and paclitaxel in chronic myeloid leukemia cells: Mcl-1 inhibition.
Abstract Paclitaxel is an alternative chemotherapeutic agent for chronic myelogenous leukemia (CML) when primary or secondary resistance of tyrosine kinase inhibitors (TKI) is emerging, because paclitaxel could bypass the apoptotic deficiencies linked to p53 and fas ligand pathways in CML. However, high levels of Bcl-2 family proteins in CML could resist paclitaxel-induced apoptosis. Herein, we utilized two BH3 mimetics ABT-737 and S1 to study the potential of BH3 mimetics in combination with paclitaxel in treatment of CML cells and illustrated the mechanism by which BH3 mimetics synergize with paclitaxel. As a si...
Source: European Journal of Pharmaceutical Sciences - January 14, 2015 Category: Drugs & Pharmacology Authors: Song T, Sheng H, Liu Y, Xie M, Chen Q, Yu X, Chai G, Zhang Z Tags: Eur J Pharm Sci Source Type: research

Simvastatin induces NFκB/p65 down-regulation and JNK1/c-Jun/ATF-2 activation, leading to matrix metalloproteinase-9 (MMP-9) but not MMP-2 down-regulation in human leukemia cells.
Abstract The aim of the present study was to explore the signaling pathways associated with the effect of simvastatin on matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia K562 cells. In sharp contrast to its insignificant effect on MMP-2, simvastatin down-regulated MMP-9 protein expression and mRNA levels in K562 cells. Simvastatin-induced Pin1 down-regulation evoked NFκB/p65 degradation. Meanwhile, simvastatin induced JNK-mediated c-Jun and ATF-2 activation. Over-expression of Pin1 suppressed simvastatin-induced MMP-9 down-regulation. Treatment with SP600125 (a JNK inhibitor) or knock-down of...
Source: Biochemical Pharmacology - October 11, 2014 Category: Drugs & Pharmacology Authors: Chen YJ, Chang LS Tags: Biochem Pharmacol Source Type: research

CXCL12/CXCR4 axis confers adriamycin resistance to human chronic myelogenous leukemia and oroxylin A improves the sensitivity of K562/ADM cells.
In conclusion, all these results showed that oroxylin A improved the sensitivity of K562/ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K/Akt/NF-κB pathway, and probably served as a most promising agent for CML treatment. PMID: 24858801 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - May 22, 2014 Category: Drugs & Pharmacology Authors: Wang Y, Miao H, Li W, Yao J, Sun Y, Li Z, Zhao L, Guo Q Tags: Biochem Pharmacol Source Type: research

Bryostatin 5 induces apoptosis in acute monocytic leukemia cells by activating PUMA and caspases.
Abstract Acute leukemia is a malignant clonal hematopoietic stem cell disease. In the current study, we examined the effects of bryostatin 5 on acute monocytic leukemia cells in vitro and in vivo. We also explored the mechanisms and pathways underlying the increase in apoptosis induced by bryostatin 5. Bryostatin 5 inhibited the growth of primary acute monocytic leukemia cells and U937 cells in a dose- and time-dependent manners. Bryostatin 5 also induced an increase in apoptosis and a decrease in the mitochondrial membrane potential (MMP) in U937 cells. Transmission electron microscopy (TEM) revealed that bryosta...
Source: European Journal of Pharmacology - September 11, 2013 Category: Drugs & Pharmacology Authors: Wang Y, Zhang J, Wang Q, Zhang T, Yang Y, Yang F, Gao G, Dong H, Zhu H, Li Y, Lin H, Tang H, Chen X Tags: Eur J Pharmacol Source Type: research

Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90.
The objective of this in vitro study was to silence inducible Hsp70 and to promote celastrol-induced tumor cell death. Hsp70 siRNA loaded chitosan-TPP carriers were prepared by ionic gelation and characterized by photon correlation spectroscopy and asymmetric flow field-flow fractionation combined with dynamic light scattering. Viability of human leukemia and glioblastoma cells and Hsp70 silencing was determined following treatment with chitosan-TPP-Hsp70 siRNA particles. The results showed that silencing of Hsp70 by chitosan-TPP-Hsp70 siRNA treatment significantly reduced cell viability, and enhanced antiproliferative eff...
Source: European Journal of Pharmaceutical Sciences - April 10, 2013 Category: Drugs & Pharmacology Authors: Matokanovic M, Barisic K, Filipovic-Grcic J, Maysinger D Tags: Eur J Pharm Sci Source Type: research

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